CN108992423A - A kind of preparation method of tamsulosin hydrochloride sustained release preparation - Google Patents

A kind of preparation method of tamsulosin hydrochloride sustained release preparation Download PDF

Info

Publication number
CN108992423A
CN108992423A CN201711109732.4A CN201711109732A CN108992423A CN 108992423 A CN108992423 A CN 108992423A CN 201711109732 A CN201711109732 A CN 201711109732A CN 108992423 A CN108992423 A CN 108992423A
Authority
CN
China
Prior art keywords
solution
tamsulosin hydrochloride
preparation
sustained release
temperature
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
CN201711109732.4A
Other languages
Chinese (zh)
Inventor
刘丽
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to CN201711109732.4A priority Critical patent/CN108992423A/en
Publication of CN108992423A publication Critical patent/CN108992423A/en
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5015—Organic compounds, e.g. fats, sugars
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5089—Processes

Landscapes

  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The present invention provides a kind of preparation method of tamsulosin hydrochloride sustained release preparation, the steps include: to be dissolved in tamsulosin hydrochloride in 95% ethyl alcohol, obtains solution A, hydroxypropylβ-cyclodextrin is added in solution A and mannitol obtains solution B；Polylactic acid and polyethylene glycol 200 are dissolved in acetone and obtain solution C, solution B and solution C are mixed into obtain solution D, solution D is transferred in magnetic stirring apparatus, continuous stirring solution D12 hours, solution D temperature is down to 0 DEG C~1 DEG C in 2 hours again and stands 12 hours, maintains solution D temperature at 0 DEG C~1 DEG C during standing.Solution D is heated after standing 12 hours, is continuously stirred when solution D temperature rises to 15 DEG C~18 DEG C, solution D temperature is controlled at 15 DEG C~18 DEG C when stirring, obtains tamsulosin hydrochloride sustained release preparation with low temperature spray drying legal system after continuously stirring 12 hours.Capsule material dosage of the present invention is moderate, and dry materials temperature is low, and obtained carrying medicine is uniform in size, and drug release is stablized, and has the characteristics that sustained release.

Description

A kind of preparation method of tamsulosin hydrochloride sustained release preparation
Technical field:
The present invention relates to a kind of pharmaceutical preparation of medicine-carrying polymer preparation more particularly to a kind of tamsulosin hydrochloride sustained release preparations Preparation method.
Background technique:
Hydroxypropylβ-cyclodextrin is a kind of ideal injection solubilizer and drug excipient in medical industry.It can be with The water solubility of insoluble drug is improved, increases medicine stability, improve drug bioavailability, the curative effect of medicament is made to increase or take Dosage is reduced, and adjustable or control drug rate of release reduces poisonous side effect of medicine.Can be used for oral drugs, injection, Mucoadhesive delivery system (including schneiderian membrane, rectum, cornea etc.), Transdermal absorption drug delivery system, lipophilicity targeted drug carrier.
Polylactic acid has tight security to human body, has good biocompatibility and biodegradability, is widely used In medicament slow release.Currently, the preparation method of polylactic acid drug bearing microsphere mainly has phase separation method, emulsion-solvent evaporation method, spray-on process Deng.
Tamsulosin hydrochloride is adrenaline a1 receptor antagonist, has selection to urethra, neck of urinary bladder and prostate smooth musculature cells Property antagonism, can reduce the prostatic part pressure in urethra inner pressure curve, and bent to rhythmic bladder contraction and intravesical pressure Line is without influence.Clinic is mainly used for treating hyperplasia of prostate and the abnormal urination symptom that causes, does not lead suitable for light, moderate patient and Cause serious urination disorder person.Constant slow release at a predetermined rate after the administration of tamsulosin hydrochloride oral slow-releasing preparation, rather than Conventional formulation can rapid delivery of pharmaceuticals.With corresponding ordinary preparation, such as fast-release tablet, capsule, oral solution is compared, and patient can be improved Compliance and increase curative effect of medication.The major advantage of sustained release preparation is can to reduce dosage frequency and avoid taking common system The blood concentration peak valley phenomenon that agent occurs.Sustained release preparation can keep blood concentration to stablize effective within the relatively long time Within the scope of blood concentration, to improve Drug safety.Tamsulosin hydrochloride sustained release preparation mainly uses skeleton agent technology at present Ethyl cellulose, acrylic resin, lactose, the auxiliary materials such as microcrystalline cellulose are commonly used in production.But it is deposited with the dosage form that such technology produces The risk that drug release changes during burst release and storage, and supplementary product consumption is big, is unfavorable for taking orally.One kind is provided to this for clinic Safely and effectively, reliable in quality, high production efficiency, supplementary product consumption is moderate, and the stable tamsulosin hydrochloride sustained release preparation of drug release is very It is necessary in consideration of it, propose the present invention.
Summary of the invention:
The technical problem to be solved by the present invention lies in overcoming the defects of the prior art, provides a kind of safe and effective, quality Reliably, high production efficiency, supplementary product consumption is moderate, the stable tamsulosin hydrochloride sustained release preparation and preparation method thereof of drug release.
The technical problems to be solved by the invention are realized using following technical scheme.
A kind of tamsulosin hydrochloride sustained release preparation, which is characterized in that the sustained release preparation is pasted by tamsulosin hydrochloride, hydroxypropyl beta-ring Essence, polylactic acid, mannitol, polyethylene glycol 200,95% ethyl alcohol and acetone composition.The tamsulosin hydrochloride sustained release preparation each group Divide by weight hydrochloric Tamsulosin 100, contain 95% ethyl alcohol 120~140, contain hydroxypropylβ-cyclodextrin 120~140, contains sweet dew Alcohol 20~30 contains acetone 120~150, contains polylactic acid 120~150, contains polyethylene glycol 200 20~40, and the polylactic acid is opposite Molecular weight is 5000~20000.
It is a further object to provide a kind of method for being prepared into tamsulosin hydrochloride sustained release preparation, feature exists In the specific steps of this method are as follows:
1) tamsulosin hydrochloride is dissolved in 95% ethyl alcohol, obtains tamsulosin hydrochloride solution, is denoted as solution A；
2) hydroxypropylβ-cyclodextrin and mannitol are added in solution A, obtains solution B；
3) polylactic acid and polyethylene glycol are dissolved in acetone, obtain polylactic acid and polyethylene glycol 200 solution, is denoted as solution C；
4) solution B and solution C are mixed, obtains solution D；
5) solution D is transferred in magnetic stirring apparatus, controls the temperature of solution D at 15 DEG C~18 DEG C, continuous stirring solution D12 hours, then solution D temperature is down to 0 DEG C~1 DEG C in 2 hours and stands 12 hours, solution D temperature is maintained during standing At 0 DEG C~1 DEG C；
6) solution D for obtaining step 5 heats, and continuously stirs when solution D temperature rises to 15 DEG C~18 DEG C 12 hours, The control of solution D temperature is at 15 DEG C~18 DEG C when stirring；
7) solution D that step 6 obtains is obtained into tamsulosin hydrochloride sustained release preparation with low temperature spray drying legal system.
Tamsulosin hydrochloride sustained release preparation of the invention passes through external tired with commercially available same dosage form tamsulosin hydrochloride sustained release preparation Product drug release amount comparative study, it was demonstrated that tamsulosin hydrochloride sustained release preparation drug release of the invention is more stable, and slow-release function is more preferable.And Preparation method high production efficiency, capsule material dosage is moderate, and dry materials temperature is low, and obtained carrying medicine is uniform in size, encapsulation rate Greater than 80%, drugloading rate is greater than 50%.
Detailed description of the invention
Curve a is the extracorporeal accumulating released medicine curve of 1 gained preparation of the embodiment of the present invention in Fig. 1, and curve b is commercially available identical The extracorporeal accumulating released medicine curve of dosage form tamsulosin hydrochloride sustained release preparation.In Fig. 1, abscissa is time (hour), ordinate For cumulative release amount (%).
Curve a is the extracorporeal accumulating released medicine curve of 2 gained preparation of the embodiment of the present invention in Fig. 2, and curve b is commercially available identical The extracorporeal accumulating released medicine curve of dosage form tamsulosin hydrochloride sustained release preparation.In Fig. 2, abscissa is time (hour), ordinate For cumulative release amount (%).
Curve a is the extracorporeal accumulating released medicine curve of 3 gained preparation of the embodiment of the present invention in Fig. 3, and curve b is commercially available identical The extracorporeal accumulating released medicine curve of dosage form tamsulosin hydrochloride sustained release preparation.In Fig. 3, abscissa is time (hour), ordinate For cumulative release amount (%).
Specific embodiment:
In order to be easy to understand the technical means, the creative features, the aims and the efficiencies achieved by the present invention, tie below Specific embodiment is closed, the present invention is further explained.
For the consistency of guarantee test result, the embodiment of the present invention has used the raw material of same batch, auxiliary material, and uses Consistent production technology prepares tamsulosin hydrochloride sustained release preparation.
Embodiment one:
1) 100g tamsulosin hydrochloride is dissolved in 120g95% ethyl alcohol, obtains tamsulosin hydrochloride ethanol solution, is denoted as solution A；
2) 120g hydroxypropylβ-cyclodextrin and 20g mannitol are added in solution A, obtains solution B；
3) 120g polylactic acid and 20g polyethylene glycol 200 are dissolved in 120g acetone, obtain polylactic acid and polyethylene glycol 200 is molten Liquid is denoted as solution C；
4) solution B and solution C are mixed, obtains solution D；
5) solution D is transferred in magnetic stirring apparatus, controls the temperature of solution D at 15 DEG C~18 DEG C, continuous stirring solution D12 hours, then solution D temperature is down to 0 DEG C~1 DEG C in 2 hours and stands 12 hours, solution D temperature is maintained during standing At 0 DEG C~1 DEG C；
6) solution D for obtaining step 5 heats, and continuously stirs when solution D temperature rises to 15 DEG C~18 DEG C 12 hours, The control of solution D temperature is at 15 DEG C~18 DEG C when stirring；
7) solution D that step 6 obtains is obtained into tamsulosin hydrochloride sustained release preparation with low temperature spray drying legal system, spray drying Temperature control is at 55 DEG C, nozzle diameter: 0.5mm, vacuum degree: 0.03MPA, flow: 500ml/ hours.
Sample obtained by low temperature spray drying is taken, it is 80.43% that gained sample, which measures encapsulation rate, carrying drug ratio 50.60%, body Outer release experiment proves that this preparation energy slow release tamsulosin hydrochloride, tamsulosin hydrochloride finally discharge up to 90% or more, see Fig. 1.
Embodiment two:
1) 100g tamsulosin hydrochloride is dissolved in 130g95% ethyl alcohol, obtains tamsulosin hydrochloride ethanol solution, is denoted as solution A；
2) 130g hydroxypropylβ-cyclodextrin and 25g mannitol are added in solution A, obtains solution B；
3) 135g polylactic acid and 30g polyethylene glycol 200 are dissolved in 135g acetone, obtain polylactic acid and polyethylene glycol 200 is molten Liquid is denoted as solution C；
4) solution B and solution C are mixed, obtains solution D；
5) solution D is transferred in magnetic stirring apparatus, controls the temperature of solution D at 15 DEG C~18 DEG C, continuous stirring solution D12 hours, then solution D temperature is down to 0 DEG C~1 DEG C in 2 hours and stands 12 hours, solution D temperature is maintained during standing At 0 DEG C~1 DEG C；
6) solution D for obtaining step 5 heats, and continuously stirs when solution D temperature rises to 15 DEG C~18 DEG C 12 hours, The control of solution D temperature is at 15 DEG C~18 DEG C when stirring；
7) solution D that step 6 obtains is obtained into tamsulosin hydrochloride sustained release preparation with low temperature spray drying legal system, spray drying Temperature control is at 55 DEG C, nozzle diameter: 0.75mm, vacuum degree: 0.035MPA, flow: 700ml/ hours.
Sample obtained by low temperature spray drying is taken, it is 80.56% that gained sample, which measures encapsulation rate, carrying drug ratio 51.16%, body Outer release experiment proves that this preparation energy slow release tamsulosin hydrochloride, tamsulosin hydrochloride finally discharge up to 90% or more, see Fig. 2.
Embodiment three:
1) 100g tamsulosin hydrochloride is dissolved in 140g95% ethyl alcohol, obtains tamsulosin hydrochloride ethanol solution, is denoted as solution A；
2) 140g hydroxypropylβ-cyclodextrin and 30g mannitol are added in solution A, obtains solution B；
3) 150g polylactic acid and 40g polyethylene glycol 200 are dissolved in 150g acetone, obtain polylactic acid and polyethylene glycol 200 is molten Liquid is denoted as solution C；
4) solution B and solution C are mixed, obtains solution D；
5) solution D is transferred in magnetic stirring apparatus, controls the temperature of solution D at 15 DEG C~18 DEG C, continuous stirring solution D12 hours, then solution D temperature is down to 0 DEG C~1 DEG C in 2 hours and stands 12 hours, solution D temperature is maintained during standing At 0 DEG C~1 DEG C；
6) solution D for obtaining step 5 heats, and continuously stirs when solution D temperature rises to 15 DEG C~18 DEG C 12 hours, The control of solution D temperature is at 15 DEG C~18 DEG C when stirring；
7) solution D that step 6 obtains is obtained into tamsulosin hydrochloride sustained release preparation with low temperature spray drying legal system,
The temperature of spray drying is controlled at 60 DEG C, and nozzle diameter: 1mm, vacuum degree: 0.04MPA, flow: 1000ml/ is small When.
Sample obtained by low temperature spray drying is taken, it is 81.29% that gained sample, which measures encapsulation rate, carrying drug ratio 51.08%, body Outer release experiment proves that this preparation energy slow release tamsulosin hydrochloride, tamsulosin hydrochloride finally discharge up to 90% or more, see Fig. 3.
The basic principles, main features and advantages of the present invention have been shown and described above.The technology of the industry For personnel it should be appreciated that the present invention is not limited to the above embodiments, described in the above embodiment and specification is only the present invention Preference, be not intended to limit the invention, without departing from the spirit and scope of the present invention, the present invention also has various Changes and improvements, these changes and improvements all fall within the protetion scope of the claimed invention.The claimed scope of the invention is by institute Attached claims and its equivalent thereof.

Claims (5)

1. a kind of preparation method of tamsulosin hydrochloride sustained release preparation, it is characterised in that the tamsulosin hydrochloride sustained release preparation is by salt Sour Tamsulosin, hydroxypropylβ-cyclodextrin, polylactic acid, mannitol, polyethylene glycol 200,95% ethyl alcohol, acetone composition.
2. the preparation method of tamsulosin hydrochloride sustained release preparation as described in claim 1, it is characterised in that the steps include:
1) tamsulosin hydrochloride is dissolved in 95% ethyl alcohol, obtains tamsulosin hydrochloride solution, is denoted as solution A；
2) hydroxypropylβ-cyclodextrin and mannitol are added in solution A, obtains solution B；
3) polylactic acid and polyethylene glycol are dissolved in acetone, obtain polylactic acid and polyethylene glycol 200 solution, is denoted as solution C；
4) solution B and solution C are mixed, obtains solution D；
5) solution D is transferred in magnetic stirring apparatus, controls the temperature of solution D at 15 DEG C~18 DEG C, continuous stirring solution D12 is small When, then solution D temperature is down to 0 DEG C~1 DEG C in 2 hours and stands 12 hours, maintain solution D temperature at 0 DEG C during standing ~1 DEG C；
6) solution D for obtaining step 5 heats, and continuously stirs when solution D temperature rises to 15 DEG C~18 DEG C 12 hours, stirs When solution D temperature control at 15 DEG C~18 DEG C；
7) solution D that step 6 obtains is obtained into tamsulosin hydrochloride sustained release preparation with low temperature spray drying legal system.
3. tamsulosin hydrochloride sustained release preparation each component as claimed in claim 1 or 2 contains by weight hydrochloric Tamsulosin 100 95% ethyl alcohol 120~140 contains hydroxypropylβ-cyclodextrin 120~140, contains mannitol 20~30, contains acetone 120~150, containing poly- Lactic acid 120~150 contains polyethylene glycol 200 20~40.
4. the preparation method of tamsulosin hydrochloride sustained release preparation as claimed in claim 1 or 2, it is characterised in that polylactic acid it is opposite Molecular weight is 5000~20000.
5. the preparation method of tamsulosin hydrochloride sustained release preparation as claimed in claim 3, it is characterised in that low temperature spray drying Temperature is 55 DEG C~60 DEG C, and nozzle diameter is 0.5mm~1mm, and hothouse vacuum degree is 0.03MPA~0.04MPA, solution D stream Amount is 500ml/ hours~1000ml/ hours.
CN201711109732.4A 2017-11-11 2017-11-11 A kind of preparation method of tamsulosin hydrochloride sustained release preparation Withdrawn CN108992423A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201711109732.4A CN108992423A (en) 2017-11-11 2017-11-11 A kind of preparation method of tamsulosin hydrochloride sustained release preparation

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201711109732.4A CN108992423A (en) 2017-11-11 2017-11-11 A kind of preparation method of tamsulosin hydrochloride sustained release preparation

Publications (1)

Publication Number Publication Date
CN108992423A true CN108992423A (en) 2018-12-14

Family

ID=64573941

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201711109732.4A Withdrawn CN108992423A (en) 2017-11-11 2017-11-11 A kind of preparation method of tamsulosin hydrochloride sustained release preparation

Country Status (1)

Country Link
CN (1) CN108992423A (en)

Similar Documents

Publication Publication Date Title
CN102933234A (en) Methods for the preparation of injectable depot compositions
WO2014040548A1 (en) Metoprolol sustained-release drug and preparation method therefor
CN108992420A (en) A kind of preparation method of salbutamol sustained release preparation
CN109010312A (en) A kind of preparation method of sustained-release theophylline preparation
CN108992394A (en) A kind of preparation method of pseudoephedrine hydrochloride slow release preparation
CN108992423A (en) A kind of preparation method of tamsulosin hydrochloride sustained release preparation
CN108992408A (en) A kind of preparation method of body of Pramipexole dihydrochloride sustained release preparation
CN108992427A (en) A kind of preparation method of Flurbiprofen sustained release preparation
CN108992409A (en) A kind of preparation method of metformin hydrochloride slow release preparation
CN109010316A (en) A kind of preparation method of vitamin B 6 sustained release preparation
CN109010277A (en) A kind of preparation method of oxycodone hydrochloride sustained release preparation
CN108992406A (en) A kind of preparation method of ropinirole hydrochloride sustained release preparation
CN109010313A (en) A kind of preparation method of alfuzosin hydrochloride sustained release preparation
CN108992421A (en) A kind of preparation method of methylphenidate hydrochloride sustained release preparation
CN108992405A (en) A kind of preparation method of Doxazosin sustained release preparation
CN109010314A (en) A kind of preparation method of indapamide slow release preparation
CN109010315A (en) A kind of preparation method of Etodolac sustained release preparation
CN104398474A (en) Nasal gel agent containing risperidone and preparation method of nasal gel agent
CN108992428A (en) A kind of preparation method of felodipine sustained-release preparation
CN109010279A (en) A kind of preparation method of venlafaxine hydrochloride sustained-release preparation
CN108992426A (en) A kind of preparation method of 9-hydroxy-risperidone sustained release preparation
CN108992410A (en) A kind of preparation method of Buflomedil Hydrochloride sustained release preparation
CN108992412A (en) A kind of preparation method of diclofenac sodium sustained release medication
CN108992461A (en) A kind of preparation method of potassium chloride sustained release preparation
CN108992424A (en) A kind of preparation method of nevirapine sustained release preparation

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
WW01 Invention patent application withdrawn after publication

Application publication date: 20181214

WW01 Invention patent application withdrawn after publication